Treatment of dyslipidemia: PCSK-9 in focus

Cardiovascular disease is the leading cause of death worldwide, accounting for one-third of the total global mortality. Dyslipidemia is one of the most common risk factors and plays a cardinal role in the development and progression of atherosclerotic cardiovascular disease. Since statin therapy is often insufficient, or cardiovascular disease continues to develop despite achieving target lipid levels, current attention is focused on new therapeutic options with significantly greater efficacy. The reduction in LDL cholesterol levels with PCSK-9 inhibitors is about 60% when used as monotherapy and as much as 85% when combined with high-intensity statins and/or other lipid-lowering therapies. Alirocumab and evolocumab are two monoclonal antibodies that effectively bind to the LDL receptor, interfering with its degradation. Inclisiran is a small interfering RNA that interferes with the synthesis of PCSK-9 molecules and effectively reduces LDL-C. Indications for PCSK-9 inhibitors usage are increasingly expanding due to the discovery of their pleiotropic effects. Additionally, the focus is on discovering new mechanisms of PCSK-9 inhibition that would open the door to the development of new therapeutic agents. Studies on the efficacy and safety of oral PCSK9 inhibitors are ongoing, along with early-stage clinical trials exploring gene-editing strategies for the treatment of dyslipidemias. The purpose of this review article is to provide an overview of the current knowledge on the application of PCSK-9 inhibitors.